BRCA1 and BRCA2 genetic testing in women with epithelial ovarian cancer

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A 62-year-old woman is evaluated during a follow-up visit for recently diagnosed stage IIIA high-grade serous ovarian cancer. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy and completed six cycles of chemotherapy with cisplatin and paclitaxel. The patient’s paternal aunt was diagnosed with breast cancer at age 52 years. There is no personal or family history of any other cancers. She takes no medications.

On physical examination, vital signs and the remainder of the examination are normal.

Laboratory studies reveal a serum CA-125 value of 14 U/mL (14 kU/L) after chemotherapy (383 U/mL [383 kU/L] at diagnosis).

Which of the following is the most appropriate test to perform next?

A. Chest radiography annually
B. CT of the abdomen and pelvis in 3 months
C. Genetic testing for BRCA1 and BRCA2 mutations
D. Genetic testing for Lynch mutations

MKSAP Answer and Critique

The correct answer is C. Genetic testing for BRCA1 and BRCA2 mutations.

This patient should be referred to a genetic counselor for genetic testing for BRCA1 and BRCA2 mutations. Current guidelines recommend BRCA1and BRCA2 genetic testing for all women with epithelial ovarian cancer, regardless of age of onset, family history, or ancestry. Of women with ovarian cancer, 10% to 15% carry a mutation in one of these genes. Approximately 75% of epithelial ovarian cancers are serous histology—the type most likely to be associated with a BRCA1 or BRCA2 mutation. This patient has a family history of breast cancer in a paternal aunt who was age 52 years, but even with no family history of breast or ovarian cancer, BRCA1 and BRCA2 genetic testing would still be recommended. Although she had her ovaries removed, positive test results for a BRCA1 or BRCA2mutation would have implications for breast cancer risk and screening, with annual mammography and breast MRI recommended. She may also consider prophylactic mastectomies. If she carries a BRCA1 or BRCA2mutation, her siblings and children have a 50% chance of inheriting the same mutation. Genetic testing is best performed by a genetic counselor, with appropriate pre- and post-test counseling.

Routine surveillance imaging studies are not recommended for monitoring patients in clinical remission after initial treatment; therefore, neither annual chest radiography nor an abdominal-pelvic CT scan in 3 months would be recommended unless the patient develops signs or symptoms suggestive of recurrent disease.

Hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant disorder caused by a germline mutation in one of the DNA mismatch repair genes. Patients with Lynch syndrome have a 3% to 14% lifetime risk of ovarian cancer, and the possibility of HNPCC mutation testing should be considered in patients with ovarian cancer. However, testing for HNPCC mutations is usually only offered to patients who have a personal or family history, or both, of additional HNPCC-related cancers, particularly colorectal, small bowel or endometrial cancers, or transitional cell cancers of the renal pelvis or ureters. This patient has no personal or family history of these cancers and would not usually be offered HNPCC testing based on her history of ovarian cancer alone. Models such as PREMM1,2,6 can be used to determine if a patient is eligible for HNPCC testing.

Key Point

Current guidelines recommend BRCA1 and BRCA2 genetic testing for all women with epithelial ovarian cancer, regardless of age of onset, family history, or ancestry.

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